Action potential modelling predicts electrophysiological and pharmacological features of human embryonic stem cell-derived cardiomyocytes.

Human embryonic stem cell-derived cardiomyocytes (hES-CM) represent a promising tool for cell therapy and drug screening. Their functional properties must be assessed. We characterized hES-CM action potentials (AP) at two developmental stages with a combination of electrophysiological, RT-PCR and modelling tools. The AP was simulated on the basis of a model of human adult ventricular cell. The model was modified to incorporate experimentally assessed stage-dependent modifications of ionic currents (e.g. f-current, If, inward rectifier, IK1, and delayed rectifier currents, IKr). Effects of current blockers were simulated by selectively reducing the current maximum conductance. As we previously showed, changes in AP occur during in-vitro maturation (Early vs. Late): increase in AP duration and amplitude, decrease of slope of diastolic depolarization and rate of spontaneous beating. AP modelling reproduces: (i) experimentally observed changes in AP profile and differential effects of IKr blockade by E4031 at Early vs. Late stages (Figure A-B); (ii) effects of Ba2+ and zatebradine (IK1 and If blockers, respectively) (Figure C-D). These results suggest that our novel mathematical model can serve as a predictive approach to interpret and refine in-vitro experiments on hES-CM.